Dr. Laguna notes that there is a need to decrease side effects in patients with testicular seminoma considering that the overall survival for CSI seminoma is 99% and that 4-12 abdominopelvic CT scans are typically used in the first 5 years of follow-up. Indeed, she notes that MRI surveillance is noted in some guidelines, but there is no high-level evidence available. As such, there are concerns for the cumulative dose of radiation and patient compliance with follow-up. TRISST is a phase III, multicenter, non-inferiority, factorial trial. Eligible men had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Randomization was to:
- 7 CTs: 6, 12, 18, 24, 36, 48, 60 months after randomization
- 7 MRIs: 6, 12, 18, 24, 36, 48, 60 months after randomization
- 3 CTs: 6, 18, 36 months after randomization
- 3 MRIs: 6, 18, 36 months after randomization
Follow-up for the trial was for 6 years with a primary outcome of 6-year incidence of stage ≥IIC relapse, aiming to exclude an increase ≥5.7% (upper limit of non-inferiority of 11.4%) with MRI (versus CT) or 3 scans (versus 7). Median follow-up was 72 months over which 82 (12%) patients relapsed, with only 10 patients relapsing with stage ≥IIC seminoma. In the intention to treat and per-protocol analysis there was non-inferiority for 3 versus 7 scans, and for MRI versus CT scan (upper 90% CI <5.7%) in primary and secondary outcomes. Dr. Laguna notes that for 4 of 9 stage >= IIC relapses in the 3-scan arms, there would have been additional opportunities for earlier detection if the patient had been in a 7-scan arm. She notes that recurrence risk is entirely based on risk factors, noting that most relapses were detected at scheduled imaging and few beyond 3 years (<1%). However, even 5 or 6 scans in the high-risk groups could be superior to 3 scans in detecting most of the 10 >= IIC relapses at an earlier stage. Dr. Laguna provided the following table assessing expected historical recurrence and the number of corresponding patients enrolled in TRISST:
Dr. Laguna then discussed the SEMS trial, noting that toxicity from treatment leads to 7-fold higher risk of all-cause mortality than the seminoma diagnosis itself for a patient diagnosed at 19 years of age and treated with radiotherapy for a stage II seminoma. Thus, it is reasonable to assess treatments that can reduce toxicity in the treatment of CSIIA/B seminoma. The SEMS trial prospectively enrolled patients (16 years of age or older) with testicular seminoma and isolated retroperitoneal lymphadenopathy between 1-3 cm in size. Open, modified-template retroperitoneal lymph node dissection (RPLND) was performed by qualified surgeons (>= 8 open RPLND in 1 year or >24 open RPLND in 3 years) with a primary endpoint of 2-year recurrence-free survival. Dr. Laguna notes that the design of this trial was excellent, focusing on the indication for the surgical intervention rather than the technique of the intervention, focusing on adverse events and potential benefit of the intervention.
There were 55 patients enrolled in SEMS and underwent RPLND. Fourteen patients had initial stage I disease who developed isolated retroperitoneal relapse while 41 patients had clinical stage IIA-B at presentation. The median age was 34 years of age (range: 21-64) with 80% of patients being white. With a median follow-up of 24 months (range: 8-52 months), there were a total of 10 recurrences. The overall recurrence rate was 18% with a median time to recurrence of 8 months; the two-year recurrence-free survival rate was 84%. Of the recurrences, eight underwent chemotherapy (6 BEP x 3, 1 EP x 4, 1 carbo/etoposide) and two underwent additional surgery.
Dr. Laguna notes that the trial concluded that primary RPLND should be considered as a treatment option for low volume metastatic seminoma should be interpreted with caution given that outcomes are comparable to the most recent literature (chemotherapy or radiation therapy), however with much shorter follow-up than the published literature. The SEMS trial will complement the PRIMETEST trial “Phase II Single-arm trial to evaluate progression-free survival with primary retroperitoneal lymph-node dissection only in patients with seminomatous testicular germ cell tumor with clinical stage IIA/B”, with an overall goal of decreasing the number of cisplatin-based chemotherapy cycles. Additionally, the 2021 EAU guidelines state that specific trials including RPLND or involved field radiation combined with a single course of carboplatin chemotherapy are addressing the role of treatment options with potentially lower toxicity compared to standard options of either radiotherapy or three cycles of BEP chemotherapy.
Dr. Laguna concluded with several key messages from these two important trials in the management of testicular seminoma:
- Both trials aim to reduce toxicity of treatment or cumulative radiation in early-stage seminoma
- Both trials are capable of improving quality of care in early-stage seminoma, as both incorporate patient and physician value and many reduce costs substantially
- TRISST will have a great impact on guideline recommendations, although when it comes to surveillance of CSI seminoma “one size does not fit all”
- SEMS is setting the stage for pursuing research for the role of RPLND in the treatment of low-volume metastatic seminoma
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021